The targeted and controlled delivery of drugs is an area of considerable current interest. The site-specific delivery of a drug to a subject is a highly desirable feature for the treatment of many different conditions. Implantation of a device comprising a drug(s) in the body of a subject (human or animal) can be desirable to improve the efficacy and safety of the drug(s). Certain sites in a subject may require sophisticated delivery devices to overcome barriers for effective drug delivery. For example, some sites have a limited volume for administration of a device and require a device that has a high dose loading to ensure the device volume is kept to a minimum. Furthermore, such devices ideally should have material properties that ensure the subject does not experience any discomfort after the implant is placed. For example, administration of a solid implant inside the synovium of a load bearing joint is likely to damage joint cartilage. One mode of delivering a drug to a subject involves the use of a polymer to carry/retain the drug to/at a specific location.
An example of such a polymer/drug delivery system utilises an admixture of a polymer with a drug, wherein the drug is blended within the polymer matrix. However, such mere admixtures generally result in poor control over the release of the drug, with a “burst effect” of drug release often occurring immediately after administration. This can lead to problems with rapid discharge of the entire dose and a significant change in the physical properties of the admixture as the drug is released. In addition, such admixtures have limited dose loading capacity resulting in a prohibitively large device for convenient administration to some sites in a subject.
A further example of a polymer/drug delivery system is based on the polymerisation of a drug(s) with other monomers (or itself) so as to incorporate the drug as part of the backbone polymer chain. Such a system is described by Uhlrich in U.S. Pat. No. 6,613,807, WO2008/128193, WO94/04593 and U.S. Pat. No. 7,122,615. However, such “polymerised” drugs also generally result in inefficient release of the drug as the release of the drug occurs via inactive intermediates. Furthermore, the resulting polymer material generally has quite poor physical properties.
Still a further example of a polymer/drug delivery system utilises a drug covalently bound to a polymer so as to form a so called polymer-drug conjugate (see Ruth Duncan Nature Reviews: Drug Discovery 2003:2, 347-360). Such polymer-drug conjugates are typically formed by covalently attaching a drug to a preformed polymer backbone. However, the synthesis of such covalently bound systems can be problematic. In particular, steric and thermodynamic constraints can affect the amount of drug that can be covalently attached, which in turn can reduce control over the release of the drug. Furthermore, there is limited scope to modify the physical properties of the resulting polymer-drug conjugate material so that it can be modified to aid comfort after administration.
Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammation. For many diseases, such as osteoarthritis, site specific delivery of the NSAID is desirable either to overcome side-effect limitations (e.g. gastro-intestinal and cardiovascular risk associated with chronic oral NSAIDs) or efficacy limitations (e.g. topical use of NSAIDs) of existing therapy (Segal, L, et al., Priority Settings in Osteoarthritis. Centre for Health Economics Report, November 2004).
An opportunity therefore remains to develop new polymer or drug delivery systems which address or ameliorate one or more disadvantages or shortcomings associated with existing systems and/or their method of manufacture, or to at least provide a useful alternative to such systems and their method of manufacture.